P1134: BISPECIFIC ANTI-CD20/19 CAR-T – ZAMTOCABTAGENE AUTOLEUCEL FOR RELAPSED/REFRACTORY DLBCL – INTERIM ANALYSIS RESULTS OF DALY-II-USA STUDY
Authors: Nirav Shah, Richard Maziarz, Caron Jacobson, Iris Isufi, Monalisa Ghosh, Matthew Ulrickson, Miguel-Angel Perales, Matthew Lunning, Nancy Hardy, Anna Wijatyk, Marek Ancukiewicz, Madhavi Nallewar, Kimberly Coleman, Bethany Prudner, Esther Eromosele, Remigiusz Kaleta, David Miklos
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: DALY II USA is the first multicenter trial of fresh, bispecific targeted CD20/CD19, chimeric antigen receptor (CAR) T-cell therapy for patients (pts) with R/R diffuse large B-cell lymphoma (DLBCL). While CD19 CAR T-cell therapy is an established treatment for pts with R/R DLBCL, relapse remains a clinical challenge. One proposed mechanism of resistance is either loss of epitope, recognition or downregulation of the CD19 receptor. To improve outcomes, dual targeting of B-cell receptor has been proposed. Reported here is the preplanned interim futility analysis after treatment of 22 evaluable pts. Aims: To assess safety and efficacy of dual CAR-T therapy with zamtocabtagene autoleucel (zamto-cel) administered fresh in R/R DLBCL Methods: Eligible pts were >18 y, ECOG PS 0-1, with R/R DLBCL after ≥2 prior lines of systemic therapy. No bridging chemotherapy was allowed. Apheresis material was shipped fresh without cryopreservation to a central manufacturing site. A fixed 12-day process of CAR-T production was performed using the CliniMACS Prodigy® (Miltenyi Biotec). A single infusion of 2.5x106 cells/kg fresh zamto-cel was administered after lymphodepletion which was initiated during manufacturing to facilitate a fresh infusion. Evaluation of response rate is the primary objective of this study. Results: As of 1 Sep 2022, 28 pts have enrolled (All treated) with 22 evaluable per protocol. Most (69%) of treated patients presented advanced disease with IPI score of at least 3 and abnormal baseline LDH and 28% were previously treated with CD19 and or CD79 targeting agents. Six pts were not included in the primary efficacy analysis. One received a frozen product and 5 received a non-conforming fresh product. Per Independent Radiology Committee (IRC) 18 (82%) of 22 evaluable pts had either complete (CR - 46%) or partial response (PR – 36%) exceeding preplanned futility threshold. Response rate in evaluable set was similar to that in all-treated population (Tbl. 1). Post progression biopsy were available in 5 pts. There was no isolated CD19 loss, but 1pt had dual target loss CD19+CD20 in relation to the pre-treatment status. PFS at 6 months for evaluable pts were 64% and 61% for all treated. The treatment was well tolerated. Among all 28 treated pts., there were no grade 3-4 CRS events and only two transient and reversible Grade 3 ICANS (9%). There were no treatment related mortality. Summary/Conclusion: Prespecified efficacy threshold of zamto-cel was exceeded in the interim analysis Treatment demonstrated a favorable safety profile, with promising ORR and PFS in advanced DLBCL population often pre-treated with agents not available in the previous similar studies. We also demonstrate the feasibility of a rapid manufacturing process with 100% fresh infusion in eligible pts. Table 1: Objective Response Rate per IRC and per Site - Evaluable Set (n=22) All Treated (n=28) IRC Per Site IRC Per Site ORR 18 (82%) 17 (77%) 22 (79%) 20 (71%) CR 10 (46%) 11 (50%) 14 (50%) 13 (46%) PR 8 (36%) 6 (27%) 8 (29%) 7 (25%) SD 1 (4%) 2 (9%) 1 (4%) 2 (7%) PD 3 (14%) 3 (14%) 5 (17%) 5 (18%) IRC – Independent Radiology Committee Keywords: Diffuse large B cell lymphoma, CD19, CAR-T, CD20